Project Summary Fetal alcohol spectrum disorders (FASD) are caused by prenatal alcohol exposure (PAE), and occur in 1-5% of the population at a cost that exceeds $4 billion dollars per year. FASD is a continuum of developmental disorders, and can result in life long disabilities. Although beneficial treatments exist, identification of affected individuals has proven difficult, and the majority of individuals with FASD are undiagnosed or misdiagnosed. There are a large number of gaps in knowledge that are critical to improvement in prevention, diagnosis and treatment for FASD. First, although PAE is the cause of FASD, it is not deterministic. A better understanding of the specific alcohol use patterns associated with specific FASD outcomes would inform prevention and intervention efforts, and support earlier diagnoses. Second, classification schema that most effectively utilizes the many physical signs associated with PAE and their contribution as markers of impaired brain development could lead to earlier and better diagnosis. Third, although several co-factors have been established as modifiers of risk for FASD, many more co-factors, mediators and modifiers remain unexplored that could substantially inform the pathophysiology and intervention efforts. Each of these knowledge gaps represent high research priorities for the prevention and treatment of FASD. The purpose of this study is to improve diagnosis of FASD through research that specifically addresses these aforementioned gaps. In a study previously funded by NIH-NIAAA, investigators formed The Collaboration on Fetal Alcohol Spectrum Disorders Prevalence consortium (CoFASP) to determine, for first time, a regionally- based prevalence estimate of FASD in four communities in the U.S. Together, these researchers developed a common protocol for the cross-sectional study design and established agreed upon classification criteria for FASD. Over 6,000 children were screened for FASD, and comprehensive data were collected on over 2,900 children for each of the relevant domains including dysmorphology; growth; cognitive, behavioral and adaptive functioning; maternal characteristics; PAE and for a subset 3D facial images. Using the CoFASP data set, we will 1) employ novel methods to elucidate exposure patterns associated with risk for PAE-related outcomes, 2) test new methodologies and diagnostic criteria as they pertain to FASD diagnosis and neurodevelopmental outcomes, and 3) investigate contextual and health-related covariates that function as mediators and/or modifiers of FASD. The advances proposed in this research allow for insights into the etiology and classification of FASD, and ultimately, factors that affect the prevalence of FASD. The investigators on this proposal are multidisciplinary, and together offer an innovative and cohesive approach to the research proposal. Through these novel approaches, we anticipate providing a foundation for future classification schema, exposure assessment and intervention strategies that are grounded in empirical evidence.